Regenerative Medicine
LUIGI P. GONZALES, MD
PGY-1
University of Washington, Department of Physical Medicine and Rehabilitation
Seattle, Washington, United States
Chris Lee, BS
Medical Student
University of California, Irvine School of Medicine
Irvine, California, United States
Arjun Gupta, n/a
Student
University of California, Irvine School of Medicine
Irvine, California, United States
Tyler Johnston, MD
Clinical Assistant Professor
Department of Orthopaedic Surgery · University of California, Irvine
Irvine, California, United States
David Wright, MD
Assistant Clinical Professor
Department of Orthopaedic Surgery · University of California, Irvine
Irvine, California, United States
Sang Ho Yoon, PhD
Researcher
Department of Anatomy & Neurobiology, UC Irvine
Irvine, California, United States
Robert Hunt, PhD
Associate Professor
Department of Anatomy & Neurobiology at UC Irvine
Irvine, California, United States
Oswald Steward, PhD
Founding Director
Reeve-Irvine Research Center for Spinal Cord Injury
Irvine, California, United States
Ranjan Gupta, MD
Professor of Orthopedics
Department of Orthopaedic Surgery · University of California, Irvine
Irvine, California, United States
LUIGI P. GONZALES, MD
University of Washington
Seattle, Washington, United States
The degradation of motor endplates (MEPs) following peripheral nerve injury (PNI) plays a major role in determining the prognosis and extent of recovery for patients. Previous studies have demonstrated the effects of stem cells in providing neurotrophic support following PNI, but their effects on the motor endplates have not been studied. We hypothesize that human-induced pluripotent stem cells (hiPSCs) differentiated into motor neuron progenitors (MNPs)would provide trophic support that prevents or limits MEP degradation following PNI. We hypothesize that human induced pluripotent stem cells (hiPSC) differentiated into motor neuron precursors would provide trophic support that prevents or limits MEP degradation following peripheral nerve injury.
Design:
Under IACUC approval, chronic denervation injury models in mice were created via sciatic nerve transection. After 4 months of denervation, the time point when MEPs have consistently degraded in this animal model, the denervated tibialis anterior (TA) of mice were injected with PBS (negative control), low dose MNPs (10,000 cells), or high dose MNPs (500,000 cells). Using a previously established method, these hiPSCs were differentiated into functional MNPs prior to injection. At select time points post-injection, the TA were harvested and stained with the appropriate antibodies to confirm MNP viability and detect the presence of MEPs.
Results:
Analysis of the muscles revealed viability and survivability of implanted MNPs. No MEPs were found in muscle injected with PBS. The low-dose group demonstrated low density of MEPs with minimal complexity, while the high-dose group revealed increased MEP density with increased morphology complexity. The contralateral, uninjured TA demonstrated high-density, healthy MEPs.
Conclusions:
MNP implantation demonstrated a dose-dependent efficacy in rescuing MEPs following PNI and could potentially serve as an adjunct to current treatment modalities for PNI.
